The causes of neuromuscular fatigue, which we define as a reduction of force-generating capacity, are poorly understood. During voluntary exercise multiple factors within both the central nervous system and the muscle fibers may contribute to force loss. We have found that the relative role played by several of these factors varies depending on the muscle groups employed and on the type of exercise from which fatigue develops. In previous studies we have measured changes in motor drive, peripheral impulse propagation and muscle metabolic states during fatigue from both sustained maximal voluntary contractions and intermittent submaximal contractions. Evidence suggests that, under some conditions, much of the force loss can be attributed to impaired excitation/contraction (e/c) coupling. So far only static contractions have been studied. We propose to continue similar studies on a wider range of muscles, but not to include both static and dynamic exercise performed at different intensities, contraction frequencies and using different duty cycles. Metabolic changes will be studied by by NMR techniques as well as by muscle biopsies. One of the main reasons for the differences seen in fatigue of different muscles depends on their relative fiber type composition. However, little is known to the contractile properties of human motor units or how they change with fatigue, since spike-triggered averaging has many well-recognized inherent errors. Thus, the contractile responses of human muscles during excercise must usually be interpreted from data obtained from animal studies. But the properties of human muscles differ in many important ways from those of cats. The problems associated with spike-triggered averaging can be overcome by recording contractions from a muscle when stimulating single motor axons in its main nerve trunk. In preliminary studies all-or none responses have been obtained from single human motor units which could be held for extended periods during which various fatiguing protocols were employed. This method provides uncontaminated data which is entirely analogous to that used on cats except that the subject is conscious and able to perform voluntary tasks. We intend to develop this technique to: a) classify the contractile properties of different human motor unit types and compare them with those of cats; b) study changes in their properties when subjected to various fatiguing protocols; c) use the data to interpret the responses of whole muscles; and d) in each fiber type to attempt to correlate the fatigue related changes in their contractile properties with those of their corresponding metabolic state, obtained from muscle biopsies.